Week 2 Articles

It is interesting to me that two papers in the same publication and year present such drastically contradicting data.  These two papers regarding the VTA dopamine neurons function in modulating depression come to two different conclusions, while being punctuated by overlapping evidence.  Tye provided evidence for dopamine’s involvement in the VTA to Nucleus Accumbens pathway and the consequential induction of a depressive phenotype with the inhibition of the DA neurons.  Chaudhury provided the data confirming the functional importance of phasic activation over tonic activation in these neurons, but found the induction of a depressive phenotype to accompany the stimulation of these specific neurons, and the opposite effects for neuronal inhibition.  Chaudhury also tested specifically how the VTA-NAc pathway and VTA-mPFC pathway are involved in promoting the susceptible and resilient phenotypes, concluding that the VTA-NAc pathway encodes reward-related stimulus in depression models.   Optogenetic phasic stimulation was used in both papers, the difference being that the Tye paper used a chronic stress model while Chaudhury employed a social defeat paradigm.  With such overlap in methods I agree that the drastic differences in conclusion seem to boil down to the models of depression/anxiety and the accompanying interpretations of data. 

Regardless of the contradiction between the two papers, they both exemplify innovative techniques that push the field forward.  The successful optogenetic stimulation of neurons is pretty groundbreaking in it’s implications, and in some ways having two papers that are sound in methodology but differ in outcomes could be what is necessary to dig deeper into the uses of this technology.  Additionally the surgical technique involving the PRV-Cre injections into the NAc and the AAV-DIO-ChR2-EYFP into the VTA to specifically express ChR2 in the VTA-NAc neurons stuck out as a nifty tool that reflects well on the innovation in neuroscience.